Swine are an important agricultural commodity and biomedical model. Manipulation of the pig genome provides opportunity to improve production efficiency, enhance disease resistance, and add value to swine products. Genetic engineering can also expand the utility of pigs for modeling human disease, developing clinical treatment methodologies, or donating tissues for xenotransplantation. Heightened interest in such models for human disease and in the production of transgenic livestock for biomedical applications have increased the need for improved methods for transgenesis, as well as for particular models of various diseases.